Two genetic loci, one dominant, Ir-Z1, the other recessive, ir-Z2, controlling immune responsiveness to aqueous solutions of Beta- galactosidase have recently been found. It is proposed to study the function of the ir-Z2 locus. First, the location of ir-Z2 and the number of genes involved will be investigated in hybrid and congenic strains. Subsequently, cell-to-cell interactions will be studied by adoptive transfer experiments and by in vitro synthesis of antibodies. The methodology developed for studying immune responsiveness to Beta- galactosidase is such that activating antibody can be detected at the single molecule level and antigen-binding cells can be easily enumerated. The objective is to establish the type of cell in which the product of the ir-Z2 gene is expressed and ultimately, to isolate and characterize the gene product.